The present invention relates to an apparatus and method for separating ions, more particularly the present invention relates to an apparatus and method for separating ions based on the ion focusing principles of high field asymmetric waveform ion mobility spectrometry (FAIMS).
High sensitivity and amenability to miniaturization for field-portable applications have helped to make ion mobility spectrometry (IMS) an important technique for the detection of many compounds, including narcotics, explosives, and chemical warfare agents as described, for example, by G. Eiceman and Z. Karpas in their book entitled xe2x80x9cIon Mobility Spectrometryxe2x80x9d (CRC, Boca Raton, 1994). In IMS, gas-phase ion mobilities are determined using a drift tube with a constant electric field. Ions are gated into the drift tube and are subsequently separated in dependence upon differences in their drift velocity. The ion drift velocity is proportional to the electric field strength at low electric field strength, for example 200 V/cm, and the mobility, K, which is determined from experimentation, is independent of the applied electric field. Additionally, in IMS the ions travel through a bath gas that is at sufficiently high pressure such that the ions rapidly reach constant velocity when driven by the force of an electric field that is constant both in time and location. This is to be clearly distinguished from those techniques, most of which are related to mass spectrometry, in which the gas pressure is sufficiently low that, if under the influence of a constant electric field, the ions continue to accelerate.
E. A. Mason and E. W. McDaniel in their book entitled xe2x80x9cTransport Properties of Ions in Gasesxe2x80x9d (Wiley, New York, 1988) teach that at high electric field strength, for instance fields stronger than approximately 5,000 V/cm, the ion drift velocity is no longer directly proportional to the applied field, and K becomes dependent upon the applied electric field. At high electric field strength, K is better represented by Kh, a non-constant high field mobility term. The dependence of Kh on the applied electric field has been the basis for the development of high field asymmetric waveform ion mobility spectrometry (FAIMS), a term used by the inventors throughout this disclosure, and also referred to as transverse field compensation ion mobility spectrometry, or field ion spectrometry. Ions are separated in FAIMS on the basis of a difference in the mobility of an ion at high field strength, Kh, relative to the mobility of the ion at low field strength, K. In other words, the ions are separated because of the compound dependent behavior of Kh as a function of the applied electric field strength. FAIMS offers a new tool for atmospheric pressure gas-phase ion studies since it is the change in ion mobility, and not the absolute ion mobility, that is being monitored.
The principles of operation of FAIMS using flat plate electrodes have been described by I. A. Buryakov, E. V. Krylov, E. G. Nazarov and U. Kh. Rasulev in a paper published in the International Journal of Mass Spectrometry and Ion Processes; volume 128 (1993), pp. 143-148, the contents of which are herein incorporated by reference. The mobility of a given ion under the influence of an electric field is expressed by: Kh=K(1+f(E)), where Kh is the mobility of an ion at high electrical field strength, K is the coefficient of ion mobility at low electric field strength and f(E) describes the functional dependence of the ion mobility on the electric field strength. Ions are classified into one of three broad categories on the basis of a change in ion mobility as a function of the strength of an applied electric field, specifically: the mobility of type A ions increases with increasing electric field strength; the mobility of type C ions decreases; and, the mobility of type B ions increases initially before decreasing at yet higher field strength. The separation of ions in FAIMS is based upon these changes in mobility at high electric field strength. Consider an ion, for example a type A ion, which is being carried by a gas stream between two spaced-apart parallel plate electrodes of a FAIMS device. The space between the plates defines an analyzer region in which the separation of ions occurs. The net motion of the ion between the plates is the sum of a horizontal x-axis component due to the flowing stream of gas and a transverse y-axis component due to the electric field between the parallel plate electrodes. The term xe2x80x9cnet motionxe2x80x9d refers to the overall translation that the ion, for instance said type A ion, experiences, even when this translational motion has a more rapid oscillation superimposed upon it. Often, a first plate is maintained at ground potential while the second plate has an asymmetric waveform, V(t), applied to it. The asymmetric waveform V(t) is composed of a repeating pattern including a high voltage component, V1, lasting for a short period of time t2 and a lower voltage component, V2, of opposite polarity, lasting a longer period of time t1. The waveform is synthesized such that the integrated voltage-time product, and thus the field-time product, applied to the plate during each complete cycle of the waveform is zero, for instance V1t2+V2t1=0; for example +2000 V for 10 xcexcs followed by xe2x88x921000 V for 20 xcexcs. The peak voltage during the shorter, high voltage portion of the waveform is called the xe2x80x9cdispersion voltagexe2x80x9d or DV in this disclosure.
During the high voltage portion of the waveform, the electric field causes the ion to move with a transverse y-axis velocity component v1=KhEhigh, where Ehigh is the applied field, and Kh is the high field ion mobility under ambient electric field, pressure and temperature conditions. The distance traveled is d1=v1t2=KhEhight2, where t2 is the time period of the applied high voltage. During the longer duration, opposite polarity, low voltage portion of the asymmetric waveform, the y-axis velocity component of the ion is v2=KElow, where K is the low field ion mobility under ambient pressure and temperature conditions. The distance traveled is d2=v2t1=KElowt1. Since the asymmetric waveform ensures that (V1t2)+(V2t1)=0, the field-time products Ehight2 and Elowt1 are equal in magnitude. Thus, if Kh and K are identical, d1 and d2 are equal, and the ion is returned to its original position along the y-axis during the negative cycle of the waveform, as would be expected if both portions of the waveform were low voltage. If at Ehigh the mobility Kh greater than K, the ion experiences a net displacement from its original position relative to the y-axis. For example, positive ions of type A travel farther during the positive portion of the waveform, for instance d1 greater than d2, and the type A ion migrates away from the second plate. Similarly, positive ions of type C migrate towards the second plate.
If a positive ion of type A is migrating away from the second plate, a constant negative dc voltage can be applied to the second plate to reverse, or to xe2x80x9ccompensatexe2x80x9d for, this transverse drift. This dc voltage, called the xe2x80x9ccompensation voltagexe2x80x9d or CV in this disclosure, prevents the ion from migrating towards either the second or the first plate. If ions derived from two compounds respond differently to the applied high strength electric fields, the ratio of Kh to K may be different for each compound. Consequently, the magnitude of the CV necessary to prevent the drift of the ion toward either plate is also different for each compound. Thus, when a mixture including several species of ions is being analyzed by FAIMS, only one species of ion is selectively transmitted for a given combination of CV and DV. The remaining species of ions, for instance those ions that are other than selectively transmitted through FAIMS, drift towards one of the parallel plate electrodes of FAIMS and are neutralized. Of course, the speed at which the remaining species of ions move towards the electrodes of FAIMS depends upon the degree to which their high field mobility properties differ from those of the ions that are selectively transmitted under the prevailing conditions of CV and DV.
An instrument operating according to the FAIMS principle as described previously is an ion filter, capable of selective transmission of only those ions with the appropriate ratio of Kh to K. In one type of experiment using FAIMS devices, the applied CV is scanned with time, for instance the CV is slowly ramped or optionally the CV is stepped from one voltage to a next voltage, and a resulting intensity of transmitted ions is measured. In this way a CV spectrum showing the total ion current as a function of CV, is obtained. It is a significant limitation of early FAIMS devices, which used electrometer detectors, that the identity of peaks appearing in the CV spectrum are other than unambiguously confirmed solely on the basis of the CV of transmission of a species of ion. This limitation is due to the unpredictable, compound-specific dependence of Kh on the electric field strength. In other words, a peak in the CV spectrum is easily assigned to a compound erroneously, since there is no way to predict or even to estimate in advance, for example from the structure of an ion, where that ion should appear in a CV spectrum. In other words, additional information is necessary in order to improve the likelihood of assigning correctly each of the peaks in the CV spectrum. For example, subsequent mass spectrometric analysis of the selectively transmitted ions greatly improves the accuracy of peak assignments of the CV spectrum.
In U.S. Pat. No. 5,420,424 which issued on May 30, 1995, B. L. Carnahan and A. S. Tarassov disclose an improved FAIMS electrode geometry in which the flat plates that are used to separate the ions are replaced with concentric cylinders, the contents of which are herein incorporated by reference. The concentric cylinder design has several advantages, including higher sensitivity compared to the flat plate configuration, as was discussed by R. W. Purves, R. Guevremont, S. Day, C. W. Pipich, and M. S. Matyjaszczyk in a paper published in Reviews of Scientific Instruments; volume 69 (1998), pp 4094-4105. The higher sensitivity of the cylindrical FAIMS is due to a two-dimensional atmospheric pressure ion focusing effect that occurs in the analyzer region between the concentric cylindrical electrodes. When no electrical voltages are applied to the cylinders, the radial distribution of ions should be approximately uniform across the FAIMS analyzer. During application of DV and CV, however, the radial distribution of ions is not uniform across the annular space of the FAIMS analyzer region. Advantageously, with the application of an appropriate DV and CV for an ion of interest, those ions become focused into a band between the electrodes and the rate of loss of ions, as a result of collisions with the FAIMS electrodes, is reduced. The efficiency of transmission of the ions of interest through the analyzer region of FAIMS is thereby improved as a result of this two-dimensional ion focusing effect.
The focussing of ions by the use of asymmetric waveforms has been discussed above. For completeness, the behavior of those ions that are not focussed within the analyzer region of a cylindrical geometry FAIMS is described here, briefly. As discussed previously, those ions having high field ion mobility properties that are other than suitable for focussing under a given set of DV, CV and geometric conditions will drift toward one or another wall of the FAIMS device. The rapidity with which these ions move towards the wall depends on the degree to which their Kh/K ratio differs from that of the ion that is transmitted selectively under the prevailing conditions. At the very extreme, ions of completely the wrong property, for instance a type A ion versus a type C ion, are lost to the walls of the FAIMS device very rapidly.
The loss of ions in FAIMS devices should be considered one more way. If an ion of type A is focussed, for example at DV 2500 volts, CV xe2x88x9211 volts in a given geometry, it would seem reasonable to expect that the ion is also focussed if the polarity of DV and CV are reversed, for instance DV of xe2x88x922500 volts and CV of +11 volts. This, however, is not observed and in fact the reversal of polarity in this manner creates a mirror image effect of the ion-focussing behavior of FAIMS. The result of such polarity reversal is that the ions are not focussed, but rather are extremely rapidly rejected from the device. The mirror image of a focussing valley is a hill-shaped potential surface. The ions slide to the center of the bottom of a focussing potential valley (2 or 3-dimensions), but slide off of the top of a hill-shaped surface, and hit the wall of an electrode. This is the reason for the existence, in the cylindrical geometry FAIMS, of the independent xe2x80x9cmodesxe2x80x9d called 1 and 2. Such a FAIMS instrument is operated in one of four possible modes: P1, P2, N1, and N2. The xe2x80x9cPxe2x80x9d and xe2x80x9cNxe2x80x9d describe the ion polarity, positive (P) and negative (N). The waveform with positive DV, where DV describes the peak voltage of the high voltage portion of the asymmetric waveform, yields spectra of type P1 and N2, whereas the reversed polarity negative DV, waveform yields P2 and N1. The discussion thus far has considered positive ions but, in general, the same principles apply to negative ions equally.
A further improvement to the cylindrical FAIMS design is realized by providing a curved surface terminus of the inner electrode. The curved surface terminus is continuous with the cylindrical shape of the inner electrode and is aligned co-axially with an ion-outlet orifice of the FAIMS analyzer region. The application of an asymmetric waveform to the inner electrode results in the normal ion-focussing behavior described above, except that the ion-focussing action extends around the generally spherically shaped terminus of the inner electrode. This means that the selectively transmitted ions cannot escape from the region around the terminus of the inner electrode. This only occurs if the voltages applied to the inner electrode are the appropriate combination of CV and DV as described in the discussion above relating to 2-dimensional focussing. If the CV and DV are suitable for the focussing of an ion in the FAIMS analyzer region, and the physical geometry of the inner surface of the outer electrode does not disturb this balance, the ions will collect within a three-dimensional region of space near the terminus. Several contradictory forces are acting on the ions in this region near the terminus of the inner electrode. The force of the carrier gas flow tends to influence the ion cloud to travel towards the ion-outlet orifice, which advantageously also prevents the trapped ions from migrating in a reverse direction, back towards the ionization source. Additionally, the ions that get too close to the inner electrode are pushed back away from the inner electrode, and those near the outer electrode migrate back towards the inner electrode, due to the focusing action of the applied electric fields. When all forces acting upon the ions are balanced, the ions are effectively captured in every direction, either by forces of the flowing gas, or by the focussing effect of the electric fields of the FAIMS mechanism. This is an example of a three-dimensional atmospheric pressure ion trap, as disclosed in U.S. Pat. No. 6,621,077, issued Sep. 16, 2003, in the name of Guevremont et al., the contents of which are herein incorporated by reference.
Ion focusing and ion trapping requires electric fields that are other than constant in space, normally occurring in a geometrical configuration of FAIMS in which the electrodes are curved, and/or are not parallel to each other. For example, a non-constant in space electric field is created using electrodes that are cylinders or a part thereof; electrodes that are spheres or a part thereof; electrodes that are elliptical spheres or a part thereof; and, electrodes that are conical or a part thereof. Optionally, various combinations of these electrode shapes are used.
As discussed above, one previous limitation of the cylindrical FAIMS technology is that the identity of the peaks appearing in the CV spectra are not unambiguously confirmed due to the unpredictable changes in Kh at high electric field strengths. Thus, one way to extend the capability of instruments based on the FAIMS concept is to provide a way to determine the make-up of the CV spectra more accurately, such as by introducing ions from the FAIMS device into a mass spectrometer for mass-to-charge (m/z) analysis. Advantageously, the ion focusing property of cylindrical FAIMS devices acts to enhance the efficiency for transporting ions from the analyzer region of a FAIMS device into an external sampling orifice, for instance an inlet of a mass spectrometer. This improved efficiency of transporting ions into the inlet of the mass spectrometer is optionally maximized by using a 3-dimensional trapping version of FAIMS operated in nearly trapping conditions. Under near-trapping conditions, the ions that have accumulated in the three-dimensional region of space near the spherical terminus of the inner electrode are caused to leak from this region, being pulled by a flow of gas towards the ion-outlet orifice. The ions that leak out from this region do so as a narrow, approximately collimated beam, which is pulled by the gas flow through the ion-outlet orifice and into a small orifice leading into the vacuum system of a mass spectrometer.
Note that, while the above discussion refers to the ions as being xe2x80x9ccapturedxe2x80x9d or xe2x80x9ctrappedxe2x80x9d, in fact, the ions are subject to continuous xe2x80x98diffusionxe2x80x99. Diffusion always acts contrary to focussing and trapping. The ions always require an electrical, or gas flow force to reverse the process of diffusion. Thus, although the ions are focused into an imaginary cylindrical zone in space with almost zero thickness, or within a 3-dimensional ion trap, in reality it is well known that the ions are actually dispersed in the vicinity of this idealized zone in space because of diffusion. This is important, and should be recognized as a global feature superimposed upon all of the ion motions discussed in this disclosure. This means that, for example, a 3-dimensional ion trap actually has real spatial width, and ions continuously leak from the 3-dimensional ion trap, for several physical, and chemical reasons. Of course, the ions occupy a smaller physical region of space if the trapping potential well is deeper.
Additionally, the resolution of a FAIMS device is defined in terms of the extent to which ions having similar mobility properties are separated under a set of predetermined operating conditions. Thus, a high-resolution FAIMS device transmits selectively a relatively small range of ion types having similar mobility properties, whereas a low-resolution FAIMS device transmits selectively a relatively large range of ion types having similar mobility properties. It is generally well known that the resolution of FAIMS in a cylindrical geometry FAIMS is compromised relative to the resolution in a parallel plate geometry FAIMS because the cylindrical geometry FAIMS has the capability of focusing and trapping ions. This focusing action means that ions of a wider range of mobility characteristics are simultaneously focused in the analyzer region of the cylindrical geometry FAIMS. A cylindrical geometry FAIMS with narrow electrodes has the strongest focusing action, but the lowest resolution for separation of ions. As the radii of curvature are increased, the focusing action becomes weaker, and the ability of FAIMS to simultaneously focus ions of similar high-field mobility characteristics is similarly decreased. This means that the resolution of FAIMS increases as the radii of the electrodes are increased, with parallel plate geometry FAIMS having the maximum attainable resolution. It is a limitation of the parallel plate FAIMS devices that are described in the prior art, however, that an ion transmitted through the analyzer region experiences a rapid change in the electric fields due to the finite size of the parallel plate electrodes. Typically, when an ion moves past the edge of the parallel plate analyzer region, the electric field that is established by the asymmetric waveform suddenly changes strength, and the ion trajectory is influenced by the applied dc potential only, causing the transmitted ion to impact with an electrode surface of the FAIMS device. It would therefore be advantageous to provide an apparatus having the high resolution property of a parallel plate FAIMS and the focusing capability and high sensitivity that are inherent in a cylindrical electrode geometry FAIMS device.
In order to overcome these and other limitations of the prior art, it is an object of the present invention to provide a high field asymmetric waveform ion mobility spectrometer for separating ions in which a transmitted ion when it exits the analyzer region experiences a balanced electric field, such that impact with one of the electrodes is prevented.
In order to overcome these and other limitations of the prior art, it is another object of the present invention to provide a high field asymmetric waveform ion mobility spectrometer for separating ions in which has a focusing effect such that the overall efficiency of ion transmission is increased.
In order to overcome these and other limitations of the prior art, it is still another object of the present invention to provide a high field asymmetric waveform ion mobility spectrometer for separating ions in which a first type of ion is selectively transmitted through a first region of an analyzer region under the influence of a first non-constant in space electric field and a second other type of ion is selectively transmitted through a second other region of the analyzer region under the influence of a second other non-constant in space electric field.
In accordance with the invention there is provided an apparatus for separating ions, comprising a high field asymmetric waveform ion mobility spectrometer, including:
a) an analyzer region comprising:
a first electrode, a second electrode and a third electrode in a spaced apart stacked arrangement for allowing ion flow therebetween, the first electrode having a first inner surface, the second electrode having a first and a second surface on opposite sides thereof, the third electrode having a second inner surface; and,
at least a contact on at least one of the first, second and third electrodes, for receiving a compensation voltage potential between the second and first electrodes and between the second and third electrodes, and for applying an asymmetric waveform to at least one of the electrodes,
wherein, in use, ions exiting from between the electrodes are other than attracted to the second electrode to collide therewith.
In accordance with the invention there is provided an apparatus for separating ions, comprising a high field asymmetric waveform ion mobility spectrometer, including:
a) an analyzer region comprising:
a first electrode, a second electrode and a third electrode in a spaced apart stacked arrangement for allowing ion flow therebetween, the first electrode having a first inner surface, the second electrode having a continuous smoothly curved surface, the third electrode having a second inner surface; and,
at least a contact on at least one of the first, second and third electrodes, for receiving a compensation voltage potential between the second and first electrodes and between the second and third electrodes, and for applying an asymmetric waveform to at least one of the electrodes,
wherein, in use, ions exiting from between the electrodes are other than attracted to the second electrode to collide therewith.
In accordance with the invention there is provided an apparatus for separating ions, comprising a high field asymmetric waveform ion mobility spectrometer, including:
a) an analyzer region comprising:
a first electrode having a first surface and a second surface on opposite sides thereof;
a second electrode absent a cross section forming a closed surface, the second electrode shaped such that a first region of the surface defines a first inner surface of the second electrode that opposes the first surface of the first electrode and a second other region of the surface defines a second inner surface of the second electrode that opposes the second surface of the first electrode; and,
at least a contact on at least one of the first and second electrodes, for applying a compensation voltage potential between the second and first electrodes, and for receiving an asymmetric waveform to at least one of the electrodes,
wherein, in use, ions exiting from between the electrodes are other than attracted to the first electrode, such that the ions other than collide therewith.
In accordance with the invention there is provided an analyzer comprising:
a first electrode having in cross section an approximately continuous periphery;
a second electrode having in cross section an approximately continuous periphery approximately equidistant from the first electrode over a region thereof and having at least an inlet for introduction of ions and a carrier gas and at least an outlet in the approximately continuous periphery; and,
a contact on at least one of the first and second electrode for providing an asymmetric electric field between the first and second electrode;
wherein, in use, ions flow through the at least an inlet about the approximately continuous periphery of the first electrode and out the at least an outlet wherein a similar electric field is present on opposing sides of the first electrode at an end proximate the at least an outlet.
In accordance with the invention there is provided a method for separating ions comprising the steps of:
a) providing at least an ionization source for producing ions including two ionic species;
b) providing an analyzer region defined by a first analyzer space between a first electrode surface and an opposing second electrode surface and a second different analyzer space between a third electrode surface and an opposing fourth electrode surface, said analyzer region being in communication with a gas inlet, a gas outlet and an ion inlet, said ions produced by said ionization source being introduced into said analyzer region at said ion inlet;
c) providing an asymmetric waveform and a direct-current compensation voltage, to at least one of said electrode surfaces, to form an electric field between the opposing pairs of electrode surfaces;
d) setting said asymmetric waveform in order to effect a difference in net displacement between said two ionic species in the time of one cycle of said applied asymmetric waveform; and,
e) setting said compensation voltage to a determined value to selectively transmit one of said two ionic species,
wherein the second electrode surface and the third electrode surface are disposed on opposing sides of a same first electrode.
In accordance with the invention there is provided a method for separating ions comprising the steps of:
a) providing at least an ionization source for producing ions including two ionic species;
b) providing two analyzer regions on opposing sides of an electrode, said two analyzer regions being in communication with a gas inlet, a gas outlet and an ion inlet, said ions produced by said ionization source being introduced into said two analyzer regions at said ion inlet;
c) forming an electric field on opposing sides of the electrode by providing an asymmetric waveform and a direct-current compensation voltage to the electrode;
d) setting said asymmetric waveform in order to effect a difference in net displacement between said two ionic species in the time of one cycle of said applied asymmetric waveform; and,
e) setting said compensation voltage to a determined value to selectively focus one of said two ionic species.